Agranulocytosis

Clozapine treatment has caused agranulocytosis,
defined as an absolute neutrophil count (ANC) less than 500/mm³.
Agranulocytosis can lead to serious infection and death. Prior to initiating
treatment with VERSACLOZ, obtain a baseline white blood cell count (WBC) and
ANC. The ANC must be greater than or equal to 2000/mm³ and the WBC must be
greater than or equal to 3500/mm³ for a patient to begin treatment with
VERSACLOZ. During treatment, patients must have regular monitoring of ANC and
WBC. Discontinue VERSACLOZ and do not rechallenge if the ANC is less than
1000/mm³ or the WBC is less than 2000/mm³. Advise patients to immediately
report symptoms consistent with agranulocytosis or infection (e.g., fever,
weakness, lethargy, or sore throat) [see DOSAGE AND ADMINISTRATION and WARNINGS
AND PRECAUTIONS].

Because of the risk of agranulocytosis, VERSACLOZ is
available only through a restricted program called the VERSACLOZ Patient
Registry. Under the VERSACLOZ Patient Registry, prescribers, patients, and
pharmacies must enroll in the program [see WARNINGS AND PRECAUTIONS].

Orthostatic Hypotension, Bradycardia, Syncope

Orthostatic hypotension, bradycardia, syncope, and
cardiac arrest have occurred with clozapine treatment. The risk is highest
during the initial titration period, particularly with rapid dose escalation.
These reactions can occur with the first dose, with doses as low as 12.5 mg per
day. Initiate treatment at 12.5 mg once or twice daily; titrate slowly; and use
divided dosages. Use VERSACLOZ cautiously in patients with
cardiovascular/cerebrovascular disease or conditions predisposing to
hypotension (e.g., dehydration, use of antihypertensive medications) [see DOSAGE
AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

Seizures

Seizures have occurred with clozapine treatment. The
risk is dose-related. Initiate treatment at 12.5 mg, titrate gradually, and use
divided dosing. Use caution when administering VERSACLOZ to patients with a
history of seizures or other predisposing risk factors for seizure (CNS
pathology, medications that lower the seizure threshold, alcohol abuse).
Caution patients about engaging in any activity where sudden loss of
consciousness could cause serious risk to themselves or others [see DOSAGE AND
ADMINISTRATION and WARNINGS AND PRECAUTIONS].

Myocarditis and Cardiomyopathy

Fatal myocarditis and cardiomyopathy have occurred
with clozapine treatment. Discontinue VERSACLOZ and obtain a cardiac evaluation
upon suspicion of these reactions. Generally, patients with VERSACLOZ-related
myocarditis or cardiomyopathy should not be rechallenged with VERSACLOZ.
Consider the possibility of myocarditis or cardiomyopathy if chest pain,
tachycardia, palpitations, dyspnea, fever, flu-like symptoms, hypotension, or
ECG changes occur [see WARNINGS AND PRECAUTIONS].

Elderly patients with dementia-related psychosis
treated with antipsychotic drugs are at an increased risk of death. VERSACLOZ
is not approved for use in patients with dementiarelated psychosis [see WARNINGS
AND PRECAUTIONS].